Abnormal connectional fingerprint in schizophrenia: a novel network analysis of diffusion tensor imaging data

The graph theoretical analysis of structural magnetic resonance imaging (MRI) data has received a great deal of interest in recent years to characterize the organizational principles of brain networks and their alterations in psychiatric disorders, such as schizophrenia. However, the characterization of networks in clinical populations can be challenging, since the comparison of connectivity between groups is influenced by several factors, such as the overall number of connections and the structural abnormalities of the seed regions. To overcome these limitations, the current study employed the whole-brain analysis of connectional fingerprints in diffusion tensor imaging data obtained at 3 T of chronic schizophrenia patients (n = 16) and healthy, age-matched control participants (n = 17). Probabilistic tractography was performed to quantify the connectivity of 110 brain areas. The connectional fingerprint of a brain area represents the set of relative connection probabilities to all its target areas and is, hence, less affected by overall white and gray matter changes than absolute connectivity measures. After detecting brain regions with abnormal connectional fingerprints through similarity measures, we tested each of its relative connection probability between groups. We found altered connectional fingerprints in schizophrenia patients consistent with a dysconnectivity syndrome. While the medial frontal gyrus showed only reduced connectivity, the connectional fingerprints of the inferior frontal gyrus and the putamen mainly contained relatively increased connection probabilities to areas in the frontal, limbic, and subcortical areas. These findings are in line with previous studies that reported abnormalities in striatal–frontal circuits in the pathophysiology of schizophrenia, highlighting the potential utility of connectional fingerprints for the analysis of anatomical networks in the disorder

Increased meso-striatal connectivity mediates trait impulsivity in FTO variant carriers

ObjectiveWhile variations in the first intron of the fat mass and obesity-associated gene (FTO, rs9939609 T/A variant) have long been identified as a major contributor to polygenic obesity, the mechanisms underlying weight gain in risk allele carriers still remain elusive. On a behavioral level, FTO variants have been robustly linked to trait impulsivity. The regulation of dopaminergic signaling in the meso-striatal neurocircuitry by these FTO variants might represent one mechanism for this behavioral alteration. Notably, recent evidence indicates that variants of FTO also modulate several genes involved in cell proliferation and neuronal development. Hence, FTO polymorphisms might establish a predisposition to heightened trait impulsivity during neurodevelopment by altering structural meso-striatal connectivity. We here explored whether the greater impulsivity of FTO variant carriers was mediated by structural differences in the connectivity between the dopaminergic midbrain and the ventral striatum.MethodsEighty-seven healthy normal-weight volunteers participated in the study; 42 FTO risk allele carriers (rs9939609 T/A variant, FTO+ group: AT, AA) and 39 non-carriers (FTO− group: TT) were matched for age, sex and body mass index (BMI). Trait impulsivity was assessed via the Barratt Impulsiveness Scale (BIS-11) and structural connectivity between the ventral tegmental area/substantia nigra (VTA/SN) and the nucleus accumbens (NAc) was measured via diffusion weighted MRI and probabilistic tractography.ResultsWe found that FTO risk allele carriers compared to non-carriers, demonstrated greater motor impulsivity (p = 0.04) and increased structural connectivity between VTA/SN and the NAc (p< 0.05). Increased connectivity partially mediated the effect of FTO genetic status on motor impulsivity.ConclusionWe report altered structural connectivity as one mechanism by which FTO variants contribute to increased impulsivity, indicating that FTO variants may exert their effect on obesity-promoting behavioral traits at least partially through neuroplastic alterations in humans

Targeting IL-17A signaling in suicidality, promise or the long arm of coincidence? Evidence in psychiatric populations revisited

Interleukin 17 (IL-17) is a potent pro-inflammatory cytokine which plays a role in autoimmune disorders, such as psoriasis and multiple sclerosis, and is important for the defense against pathogens, particularly in the gut. However, IL-17 has recently also gained attention in association with suicidal behavior. In this review, we review the literature regarding IL-17 in psychiatric disorders and suicidality. We also take a closer look at the suicides which occurred in the clinical trial for psoriasis with brodalumab, a monoclonal antibody targeting the IL-17 receptor. Lastly, we discuss potential working mechanisms relevant to neuroinflammation and the possible involvement of IL-17

Akute psychotische Störung als erste klinische Manifestation einer Multiplen Sklerose – eine Kasuistik

Background!#!The fiberoptic endoscopic evaluation of swallowing (FEES) is considered to be an indispensable instrumental procedure in the management of patients with dysphagia. The aim of the implemented training curriculum is to raise the quality standards and to contribute to an upgrading of the procedure.!##!Objective!#!The study evaluated to what extent a standardized implementation, evaluation and documentation of FEES takes place in Germany after the introduction of the curriculum.!##!Material and methods!#!In this study 603 neurological and geriatric hospitals in Germany were interviewed by the use of an online questionnaire regarding structural features and the course of the investigation.!##!Results!#!A total of 190 institutions completed the survey. Of the institutions 43.31% had only implemented FEES since the publication of the curriculum. The practical application is increasingly carried out by physicians (59%), the clinical reports and cost recommendations are carried out by speech therapists (62% and 83%, respectively). The practical application by speech therapists increases with increasing level of training. Despite orientation towards the standard protocol according to Langmore, there are differences in the implementation of the anatomical physiological examination, the consistencies and foods administered and the scoring of swallowing-relevant parameters.!##!Discussion!#!The introduction of the curriculum has led to an upgrading of the FEES and to a strengthening of speech therapy as the implementing professional group. At the current state of the art there is a homogeneous course of the examination in essential aspects but it shows a need for further uniformity. The FEES curriculum could be used as a guiding instrument for further standardization

Atypical Autoimmune Encephalitis With Neuropil Antibodies Against a Yet Unknown Epitope

Autoimmune encephalitis often causes acute psychiatric symptoms and epileptic seizures. However, it is becoming increasingly clear that depending on the target antigen both symptoms and disease severity may vary. Furthermore, the identification and characterization of antibody subtypes are highly relevant for personalizing the treatment and to prevent relapses. Here we present an atypical case of encephalitis with cerebellar and temporal dysfunction but without seizures associated with high levels of cerebrospinal fluid neuropil antibodies against a yet unknown epitope on the neuronal surface in the cerebellum, hippocampus, thalamus, and the olfactory bulb. We treated the patient successfully with corticosteroids, plasmapheresis, and rituximab

Technical Note: Modulation of fMRI brainstem responses by transcutaneous vagus nerve stimulation

Our increasing knowledge about gut-brain interaction is revolutionising the understanding of the links between digestion, mood, health, and even decision making in our everyday lives. In support of this interaction, the vagus nerve is a crucial pathway transmitting diverse gut-derived signals to the brain to monitor of metabolic status, digestive processes, or immune control to adapt behavioural and autonomic responses. Hence, neuromodulation methods targeting the vagus nerve are currently explored as a treatment option in a number of clinical disorders, including diabetes, chronic pain, and depression. The non-invasive variant of vagus nerve stimulation (VNS), transcutaneous auricular VNS (taVNS), has been implicated in both acute and long-lasting effects by modulating afferent vagus nerve target areas in the brain. The physiology of neither of those effects is, however, well understood, and evidence for neuronal response upon taVNS in vagal afferent projection regions in the brainstem and its downstream targets remain to be established. Therefore, to examine time-dependent effects of taVNS on brainstem neuronal responses in healthy human subjects, we applied taVNS during task-free fMRI in a single-blinded crossover design. During fMRI data acquisition, we either stimulated the left earlobe (sham), or the target zone of the auricular branch of the vagus nerve in the outer ear (cymba conchae, verum) for several minutes, both followed by a short ‘stimulation OFF’ period. Time-dependent effects were assessed by averaging the BOLD response for consecutive 1-minute periods in an ROI-based analysis of the brainstem. We found a significant response to acute taVNS stimulation, relative to the control condition, in downstream targets of vagal afferents, including the nucleus of the solitary tract, the substantia nigra, and the subthalamic nucleus. Most of these brainstem regions remarkably showed increased activity in response to taVNS, and these effect sustained during the post-stimulation period. These data demonstrate that taVNS activates key brainstem regions, and highlight the potential of this approach to modulate vagal afferent signalling. Furthermore, we show that carry-over effects need to be considered when interpreting fMRI data in the context of general vagal neurophysiology and its modulation by taVNS

The role of insulin sensitivity and intranasally applied insulin on olfactory perception

Olfactory perception determines food selection behavior depending on energy homeostasis and nutritional status. The mechanisms, however, by which metabolic signals in turn regulate olfactory perception remain largely unclear. Given the evidence for direct insulin action on olfactory neurons, we tested olfactory performance (olfactory threshold, olfactory discrimination) in 36 subjects of normal- and overweight after administration of three different insulin doses (40 I.U., 100 I.U., 160 I.U.) or corresponding placebo volume in a within-subject design. Poor peripheral insulin sensitivity as quantified by HOMA-IR in baseline condition and increases in systemic insulin levels reactive to intranasal administration predicted poor olfactory performance. In contrast, intranasal insulin enhanced odor perception with a dose-dependent improvement of olfactory threshold. These findings indicate a new diametric impact of insulin on olfactory perception depending on peripheral or central availability

Technical Note: Modulation of fMRI brainstem responses by transcutaneous vagus nerve stimulation

Our increasing knowledge about gut-brain interaction is revolutionising the understanding of the links between digestion, mood, health, and even decision making in our everyday lives. In support of this interaction, the vagus nerve is a crucial pathway transmitting diverse gut-derived signals to the brain to monitor of metabolic status, digestive processes, or immune control to adapt behavioural and autonomic responses. Hence, neuromodulation methods targeting the vagus nerve are currently explored as a treatment option in a number of clinical disorders, including diabetes, chronic pain, and depression. The non-invasive variant of vagus nerve stimulation (VNS), transcutaneous auricular VNS (taVNS), has been implicated in both acute and long-lasting effects by modulating afferent vagus nerve target areas in the brain. The physiology of neither of those effects is, however, well understood, and evidence for neuronal response upon taVNS in vagal afferent projection regions in the brainstem and its downstream targets remain to be established. Therefore, to examine time-dependent effects of taVNS on brainstem neuronal responses in healthy human subjects, we applied taVNS during task-free fMRI in a single-blinded crossover design. During fMRI data acquisition, we either stimulated the left earlobe (sham), or the target zone of the auricular branch of the vagus nerve in the outer ear (cymba conchae, verum) for several minutes, both followed by a short 'stimulation OFF' period. Time-dependent effects were assessed by averaging the BOLD response for consecutive 1-minute periods in an ROI-based analysis of the brainstem. We found a significant response to acute taVNS stimulation, relative to the control condition, in downstream targets of vagal afferents, including the nucleus of the solitary tract, the substantia nigra, and the subthalamic nucleus. Most of these brainstem regions remarkably showed increased activity in response to taVNS, and these effect sustained during the post-stimulation period. These data demonstrate that taVNS activates key brainstem regions, and highlight the potential of this approach to modulate vagal afferent signalling. Furthermore, we show that carry-over effects need to be considered when interpreting fMRI data in the context of general vagal neurophysiology and its modulation by taVNS